Research Abstract

One theme central to our work is understanding olfactory dysfunction at both more central and peripheral levels. To this end, psychophysical instruments and MR imaging techniques will be developed. Unfortunately, evaluation of olfactory dysfunction at the site of initial transduction at the mucosal level is by inference only. Currently, we evaluate the mucosa with olfactory biopsies and through direct visualization with endoscopy. Olfactory biopsies provide limited information because of their inherent nature of sampling a small area of the mucosa that may not reflect the over-all pathology. Traditional endoscopy may reveal gross anatomical features, but tells nothing of function. A technique that could monitor the initial olfactory transduction events across a large portion of the mucosa may shed light on both basic mechanisms of olfactory function and dysfunction. Functional optical imaging, coupled with video technology, offers such a possibility. The major objective is, therefore, to develop a high resolution, odor induced, functional map of in vivo human olfactory mucosa using an intrinsic reflection signal. Besides shedding light on olfactory function and dysfunction, functional imaging of the olfactory mucosa will help direct olfactory biopsies and guide surgery for patients with phantosmia.

The aim of our project is to test the hypothesis that odorant-specific mucosal activity patterns are projected to the bulb and to behavior in some orderly fashion and so serve as the basis for olfactory discrimination. The overall strategy is first to document conditions that vary the mucosal activity patterns and then, using these conditions, determine: 1) how these changes in the mucosal patterns project, if at all, as activity changes in the bulb, and 2) how these changes in activity patterns at both the mucosal and bulbar levels affect, if at all, the animal''s ability to discriminate behaviorally among the odorants. Four different approaches will be used to change the spatial activity patterns across the mucosa.

One approach will be to mix two odorants in stepwise proportions expecting the mucosal activity pattern to change from that given by one odorant alone to that given by the other odorant alone. In a second approach a given odorant''s mucosal activity pattern will be altered by adapting the receptors to the same and different odorants. In the third approach, odorants in homologous series will be presented in systematic increments expecting the mucosal activity patterns to change. In the final approach, a given odorant''s mucosal activity pattern will be altered by changing the odorant''s flow rate, flow path and flow direction through the nasal cavity. These various alterations in mucosal patterns were chosen so as to give a comprehensive evaluation of whether the odorant-specific activity patterns at the mucosa and the bulb are related in some systematic fashion to each other and to determine, at long last, whether these activity patterns play a significant role in the neural encoding of different odorants. A breakdown in this coding process could likely play a pivotal role in a number of human olfactory dysfunctions.